63 research outputs found

    Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

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    Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns.We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (P<0.001). Western blot concurred in determining that EONS babies had conspicuous Hp&HpRP bands in cord blood ("switch-on pattern") as opposed to non-EONS newborns who had near-absent "switch-off pattern" (P<0.001). Fetal Hp phenotype independently impacted Hp&HpRP. A bayesian latent-class analysis (LCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage.Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth

    How robust are community-based plant bioindicators? Empirical testing of the relationship between Ellenberg values and direct environmental measures in woodland communities

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    There are several community-based bioindicator systems that use species presence or abundance data as proxies for environmental variables. One example is the Ellenberg system, whereby vegetation data are used to estimate environmental soil conditions. Despite widespread use of Ellenberg values in ecological research, the correlation between bioindicated values and actual values is often an implicit assumption rather than based on empirical evidence. Here, we correlate unadjusted and UK-adjusted Ellenberg values for soil moisture, pH, and nitrate in relation to direct environmental measures for 50 woodland sites in the UK, which were subject to repeat sampling. Our results show the accuracy of Ellenberg values is parameter specific; pH values were a good proxy for direct environmental measures but this was not true for soil moisture, when relationships were weak and non-significant. For nitrates, there were important seasonal differences, with a strong positive logarithmic relationship in the spring but a non-significant (and negative) correlation in summer. The UK-adjusted values were better than, or equivalent to, Ellenberg’s original ones, which had been quantified originally for Central Europe, in all cases. Somewhat surprisingly, unweighted values correlated with direct environmental measures better than did abundance-weighted ones. This suggests that the presence of rare plants can be highly important in accurate quantification of soil parameters and we recommend using an unweighted approach. However, site profiles created only using rare plants were inferior to profiles based on the whole plant community and thus cannot be used in isolation. We conclude that, for pH and nitrates, the Ellenberg system provides a useful estimate of actual conditions, but recalibration of moisture values should be considered along with the effect of seasonality on the efficacy of the system

    Genome-wide association and functional follow-up reveals new loci for kidney function

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    Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

    Beyond equilibrium climate sensitivity

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    ISSN:1752-0908ISSN:1752-089

    Multidecadal variability of summer temperature over Romania and its relation with Atlantic Multidecadal Oscillation

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    We investigate the multidecadal variability of summer temperature over Romania as measured at 14 meteorological stations with long term observational records. The dominant pattern of summer temperature variability has a monopolar structure and shows pronounced multidecadal variations. A correlation analysis reveals that these multidecadal variations are related with multidecadal variations in the frequency of four daily atmospheric circulation patterns from the North Atlantic region. It is found that, on multidecadal time scales, negative summer mean temperature (TT) anomalies are associated with positive sea level pressure (SLP) anomalies centered over the northern part of the Atlantic Ocean and Scandinavia and negative SLP anomalies centered over the northern part of Africa. It is speculated that a possible cause of multidecadal fluctuations in the frequency of these four patterns are the sea surface temperature anomalies associated to the Atlantic Multidecadal Oscillation. These results have implications for predicting the evolution of summer temperature over Romania on multidecadal time scales

    Revisiting the region: 'ordinary' and 'exceptional' regions in the work of Hilda Ormsby 1917-1940

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    Increased interest in and recognition of the value of the region and particularly the 'ordinary region' as opposed to more-glamorous 'exceptional regions'. encourages us to reexplore the nature and purpose of what could be described as the first methodological blueprint of modern British geographical enquiry. Received histories of geography which give the impression of the production of geographical knowledge as a (near) universal male domain and the post-1960s critique of the regional approach as descriptive and nonhermeneutical have combined to make invisible the geographical work of most women (and some men) working in British universities in the first half of the 20th century. Despite this, insights can clearly be gained from biographical studies of both 'ordinary' geographers like Hilda Ormsby and the epistemology of the 'ordinary region'. This allows for a richer and more-nuanced critical historiography of geography, but there is also a potentially fruitful reciprocity in conversation between that history of geographical ideas and explorations of economic alterity. Regional studies which may have been dismissed as 'merely descriptive' can be found to articulate detailed accounts of local socioeconomic practices giving evidence of the historical grounding for current economic standing, including complex and sometimes resistant interaction with dominant modes of economic 'success'
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